This invention relates generally to medical devices and methods, and more particularly to systems and methods for avoiding or reducing substance-induced renal damage.
Numerous drugs and other substances are known to be nephrotoxic. For example, radiographic contrast media (e.g., xe2x80x9ccontrast agentxe2x80x9d orxe2x80x9cdyexe2x80x9d), non-steroidal antiinflamatory drugs (NSAID""s), amphotericin, cisplatin, methotrexate, acyclovir, gentamicin, acetylcholinesterase inhibitiors, other nephrotoxic drugs, products of tumor lysis and products of rhabdomyolysis are known to cause damage to the kidneys.
In particular, radiologic contrast media (sometimes referred to as contrast agents or dyes) are frequently administered to patients undergoing radiographic investigations, such as fluoroscopy, X-ray, magnetic resonance and ultrasound imaging, to visualize blood vessels or blood flow and/or to enhance the image being obtained. For example, contrast medium may be administered to patients undergoing coronary angiography or other cardiac catheterization procedures. Delivery of the contrast media into a patient""s vasculature enables the vasculature of different organs, tissue types, or body compartments to be more clearly observed or identified.
However, the use of radiographic contrast media may be associated with adverse side effects, including nephrotoxicity. In particular, contrast medium-induced nephrotoxicity is known to be an iatrogenic cause of acute renal failure in some patients. It has been reported that use of contrast media is the third most common cause of new onset renal failure in hospital patients. Patients who experience nephrotoxicity may experience changes in serum creatinine, or creatine clearance, at about one to five days after receiving the contrast medium. Consequences may be dramatic and can lead to irreversible renal damage and dialysis.
Acute deterioration in renal function is a recognized complication after coronary angiography, particularly for patients with pre-existing renal insufficiency. For patients with abnormal baseline renal function, the incidence of progressive renal deterioration may be as high as 42%. For hospitalized, critically ill patients, these results carry a poor prognosis for the patient, especially if dialysis becomes necessary. Factors that may predispose a patient for developing acute renal failure include, pre-existing renal insufficiency, diabetes mellitus, cardiovascular disease, including congestive heart failure, aging, and conditions characterized by depletion of effective circulatory volume.
Several mechanisms have been suggested for contrast medium-induced nephropathy. After radiographic contrast medium exposure, a brief period of vasodilation may be followed by renal vasoconstriction leading to intense reduction in renal blood flow, direct toxicity to renal tubular epithelium, tubular obstruction by protein precipitates, complement activation, and renal ischemia. In addition, patients at high risk of developing renal failure, including those with endothelial dysfunction, may not be able to dilate the renal vasculature, and thus experience a prolonged vasoconstrictive response. Vasoconstriction not only causes a decrease in renal blood flow and glomerular filtration rate, but it may also exacerbate medullary ischemia by decreasing oxygen supply since renal oxygen consumption is coupled to renal blood flow.
Attempts to reduce or prevent contrast medium-induced renal failure have included periprocedural hydration, forced diuresis, blood volume expansion, low osmolality versus high osmolality contrast agents, dopamine, calcium channel blockers, mannitol, atrial natriuretic peptide, acetylcholine esterase (ACE) inhibitors, the adenosine antagonist theophylline, endothelin receptor antagonists, and acetylcysteine. The attempts have generally been directed to reduce vasoconstriction and the negative effects that may be associated with vasoconstriction, such as the exacerbation of medullary ischemia. See, Renal Preservation Strategies for High Risk Patients, University of Chicago Prizker School of Medicine, (August 2000).
Mild hypothermia (e.g., approximately 32 degrees Celsius to approximately 36 degrees Celsius) has been shown to reduce metabolic requirements of organs, such as the heart and/or the brain. Indeed, if the hypothermia is systemic, the metabolic demands of the entire body may be reduced, so that the demands placed on the heart may be reduced. Hypothermia may also be effective to reduce ischemia in specific organs and to reduce the potential of organ damage due to such ischemia.
The physiology of hypothermia is fairly well understood. Normal human body temperature (approximately 37 degrees Celsius) may vary by approximately one degree Celsius. As body temperature decreases, resting muscle tone increases to attempt to generate heat, and the peripheral circulation is reduced to decrease blood flow to the skin to attempt to reduce heat loss. Shivering may develop as the body attempts to increase the metabolism and generate heat. When the temperature of the body decreases to approximately 35 degrees Celsius, shivering may be maximal. Below approximately 31 degrees Celsius, oxygen consumption may drop and shivering may cease. Patients with body temperatures below 27 degrees Celsius may be classified as severely hypothermic, and may be characterized by the cessation of voluntary movement, less than half normal cardiac output, and a significant risk of ventricular fibrillation.
One method for inducing hypothermia of a patient is through the use of a heat exchange catheter that is inserted into a blood vessel and used to cool blood flowing through that blood vessel. This method in general is described in U.S. Pat. No. 6,110,168 (Ginsburg), which is expressly incorporated herein by reference. Various heat exchange catheters useable for achieving the endovascular cooling are described in U.S. Pat. No. 5,486,208 (Ginsburg), PCT International Publication WO 00/10494 (Machold et al.), U.S. Pat. No. 6,264,679 (Keller et al.), PCT International Publication WO 01/58397, all of which are expressly incorporated herein by reference.
As indicated above, the potential for shivering is present whenever a patient is cooled below that patient""s shivering threshold, which in humans is generally about 35.5xc2x0 C. When inducing hypothermia below the shivering threshold, it is important to avoid or limit the shivering response in the patient. The avoidance or limiting of the shivering response may be particularly important in patients who suffer from compromised cardiac function and/or metabolic irregularities. An anti-shivering treatment may be administered to prevent or deter shivering. Examples of effective anti-shivering treatments are described in U.S. Pat. No. 6,231,594 (Dae et al.), the content of which is hereby incorporated by reference.
Thus, there remains a need in the art for improving patient outcome and organ preservation in patients that are administered contrast media, including patients who may be predisposed to developing acute renal failure induced by contrast media.
The present invention provides methods and systems wherein an endovascular heat exchange device is used to cool all or a portion of the body of a human or veterinary patient to prevent the occurrence of, or to reduce the severity of, renal damage that may result from blood-borne nephrotoxic substances, such as; radiographic contrast media (e.g., xe2x80x9ccontrast agentxe2x80x9d or xe2x80x9cdyexe2x80x9d), non-steroidal antiinflamatory drugs (NSAID""s), amphotericin, cisplatin, methotrexate, acyclovir, gentamicin, acetylcholinesterase inhibitiors, other nephrotoxic drugs, products of tumor lysis and products of rhabdomyolysis, etc. The method of the present invention is generally performed by inserting an endovascular heat exchange device into the vasculature of the patient and using such heat exchange device to cool all or a portion of the patient""s body (e.g., at least the patient""s kidneys) to a temperature at which the substance-induced renal damage is prevented or attenuated. The endovascular heat exchange device may be controlled by an automated controller that regulates the amount of heat exchanged by the heat exchanger to maintain the temperature of the renal parenchyma or kidney tissue (or the patient""s core body temperature) within a temperature range that is optimal for reducing or avoiding the substance-induced renal damage.
In accordance with one specific embodiment of the invention, there is provided a method of reducing kidney damage resulting from administration of radiographic contrast medium to a human or veterinary patient. This method generally comprises the steps of a) positioning an endovascular heat exchange device in a blood vessel of the patient, and b) using the endovascular temperature exchange device to lower the temperature of the patient""s body or at least the patient""s kidneys to a temperature at which the nephrotoxic effect of the radiographic contrast medium is lessened or eliminated.
In accordance with other specific embodiments of the invention, there are provided methods for preventing or reducing the renal damage that occurs due to an overdose of a nephrotoxic drug (e.g., NSAID overdose), administration of a nephrotoxic drug to a patient whose kidney function is already impaired or other ingestion, absorption, formation or exposure of/to a nephrotoxic substance. This method generally comprises the steps of a) positioning an endovascular heat exchange device in a blood vessel of the patient, and b) using the endovascular temperature exchange device to lower the temperature of the patient""s body or at least the patient""s kidneys to a temperature at which the nephrotoxic effect of drug or other nephrotoxic substance is lessened or eliminated.
Still further in accordance with the invention, the endovascular heat exchange device may comprise a heat exchange catheter that is insertable into the vasculature of the patient. Such heat exchange catheter may have a discrete heat exchanger (e.g., a heat exchange region or heat exchange surface) that occupies less than the entire length of the catheter. The heat exchanger may be a flowing fluid type of heat exchanger wherein a thermal exchange fluid such as heated or cooled saline solution or water is circulated. In this regard, the heat exchange catheter may be in fluid communication with extracorporeal device(s) that control the temperature of and pump thermal exchange fluid (e.g., saline solution or water) through a heat exchanger located on the portion of the catheter that is positioned in the patient""s vasculature. A programmable controller may be provided to control and maintain the temperature of all or a portion of the patient""s body within a desired hypothermic, nephrotoxicity-reducing temperature range such as 32-36xc2x0 C.
Still further in accordance with the invention, the foregoing methods may be practiced by positioning the endovascular heat exchange device in the blood vessel so that blood flows past or around the device, thereby cooling the blood that perfuses the patient""s kidneys and, thus, cooling the kidneys themselves. The endovascular heat exchange device may comprises an inflatable balloon, either single lobed or multi-lobed, and/or may comprise a metallic surface capable of transferring heat. When inflatable balloons are utilized, the balloons may be inflated after being inserted into the patient. The balloons may be inflated by passing fluid, such as heat exchange fluid, through the lumens of the balloon, or may be inflated by passing gas through the balloon.
Still further in accordance with the invention, the foregoing methods may also include a step of disrupting the laminarity of blood flow around the endovascular heat exchange device. Such blood flow disruption may be caused by one or more flow disruptors (e.g., fins, projections, indentations, ridges, grooves, troughs, knobs, bumps, etc.) formed on or near the blood contacting surface of the endovascular heat exchange device. In addition, the flow disruption may be obtained by configuring the heat exchange device in a manner to alter the flow of blood around the device. For example, the lumens or lobes of a heat exchange balloon may be helically arranged around the shaft of a catheter.
The foregoing methods may also include a step of maintaining the reduced temperature for a sufficient time to reduce nephrotic side effects caused by the contrast medium. The patient""s temperature may be reduced prior to the administration of the contrast medium, and may be maintained during and after the administration of the contrast medium.
The body temperature may be reduced to a temperature below 37 degrees Celsius, and in some instances, the patient""s temperature will be reduced to between 32 degrees and 37 degrees Celsius. Because shivering may occur when the temperature of the patient is lowered, the methods may be practiced with a step of administering an anti-shivering mechanism to the patient. The anti-shivering mechanism may be a blanket, and/or it may be a pharmaceutical agent.
The foregoing methods may also include a step or steps of monitoring the patient""s temperature, and adjusting the patient""s temperature based on the monitored temperature.
In accordance with the disclosure herein, a medical system for reducing nephrotic injury induced by contrast medium that is administered to a patient may comprise an endovascular heat exchange catheter, and a temperature controller in communication with the catheter to cause a controlled temperature change of the heat exchange catheter that is sufficient to reduce the temperature of the patient""s kidneys to reduce injury of the kidneys caused by the contrast medium. The heat exchange catheter may include a heat exchange balloon that receives heat exchange fluid from the temperature controller. The heat exchange balloon may be disposed about the catheter to direct the heat exchange fluid in an opposite direction of the blood flowing around the catheter. The temperature controller of the medical system may include temperature monitoring means and temperature adjusting means. The temperature monitoring means and the temperature adjusting means may be integrally provide with the controller, or may be separate components. The medical system may also include an anti-shivering mechanism that may be used to reduce shivering in the patient caused by the lowering of the patient""s temperature.